BLOC1S3

Summary: Human BLOC1S3 loss causes developmental ocular abnormalities.

Reason: PMID:16385460 reports foveal hypoplasia and optic pathway misrouting in affected family members. Retain this developmental phenotype as non-core; the primary molecular role is organelle cargo sorting, rather than a dedicated eye-development program. The human findings differ from the reported mouse eye-pigmentation phenotype.

Summary: BLOS3 associates with the BLOC-1 subunit BLOS2.

Reason: The source identifies Q6QNY1 (BLOC1S2), and the canonical UniProt record independently specifies direct BLOS2 interaction with three recorded experiments. PMID:15102850 establishes BLOS3 in the BLOC-1 interaction network. This is a supported physical association, retained outside the core molecular synthesis. Neither this pair nor the whole-octamer structure establishes a more specific molecular activity of the isolated pair; AP-3 complex association is a separate assertion, not a replacement for the BLOS2 interaction.

Summary: A cytoplasmic pool is consistent with soluble BLOC-1.

Reason: This combined electronic assertion uses mouse Q5U5M8 and subcellular-location mapping. The human complex has soluble and membrane-associated pools; the broad cytoplasm term is compatible but less informative than the supported cytosolic complex membership.

Summary: BLOS3 participates in cytosolic BLOC-1 complexes.

Reason: The mouse orthology transfer agrees with biochemical co-fractionation of human and mouse BLOS3 in PMID:15102850 and the cytosolic BLOC-1 pool examined in PMID:16837549. Cytosol is compatible with reversible association of assembled BLOC-1 with endosomal membranes.

Summary: Reactome places BLOC-1 assembly in the cytosol.

Reason: Retain the Reactome cytosolic localization, consistent with the soluble BLOC-1 complex characterized biochemically. The cached event summary is brief; the localization judgment also uses PMID:15102850 and the soluble/membrane fractionation in PMID:16837549.

Summary: Conserved BLOC-1 can support neuronal cargo delivery.

Reason: This Ensembl transfer from Q5U5M8 concerns a contextual neuronal role. The historical donor record cites PMID:21998198, whose selected Results and Methods test dysbindin-, muted- and pallidin-deficient mouse neurons and AP-3-dependent PI4KIIalpha targeting. Retain a conserved complex-level role without calling these direct human BLOS3 experiments or assigning BLOS3 motor activity.

Summary: The manual mouse-to-human transfer is plausible at complex level.

Reason: The inspected neuronal experiments in PMID:21998198 support cargo sorting from neuronal cell bodies into processes by BLOC-1 and AP-3. BLOS3 is a conserved component, so the ISS is biologically defensible as a contextual role. The current donor graph and a BLOS3-specific neuronal perturbation were not established; this is not direct evidence of BLOS3-driven axonal motility.

Summary: Endosomal cargo sorting does not establish protein passage across a membrane.

Reason: GO:0008320 describes transfer of a protein between opposite sides of a membrane. The inspected PMID:16837549 endosomal fractionation and association experiments, together with BLOS3 complementation and cargo sorting in PMID:17182842, instead concern delivery of membrane cargo between compartments. They do not demonstrate translocation of a protein across a lipid bilayer. This mechanistic mismatch supports removing the electronic assignment. The current mouse donor assertion was not recovered; the decision does not depend on a historical wiki flag or claim that the donor annotation has been deleted.

Summary: The exact transport-vesicle localization assertion remains unresolved.

Reason: PMID:17182842 includes human BLOS3 re-expression in mouse melan-rp cells and localizes reconstituted BLOC-1 in MuHA-rescued cells to tubulovesicular structures near the Golgi, melanosomes and endosomal vacuoles (Results, Supplemental Figure S3b/c). This supports complex-associated endosomal localization. The recovered article body does not identify the precise BLOS3 experiment underlying this IDA transport-vesicle assignment, and the relevant figure images and supplements were not inspected. Retain UNDECIDED without inferring a wrong-gene error or treating Tyrp1 cargo labeling as BLOS3 labeling.

Summary: Platelet dysfunction is a supported consequence of human BLOC1S3 deficiency.

Reason: The human family and selected platelet aggregation/secretion experiments in PMID:16385460 support this physiological annotation. Keep it non-core: BLOS3 contributes to lysosome-related organelle biogenesis, and the impaired activation phenotype does not identify an independent receptor-signaling or catalytic activity.

Summary: PAINT complex membership agrees with direct human BLOS3 evidence.

Reason: The IBA through PTN001592525 is consistent with the conserved BLOC-1 subunit and independent human biochemical evidence. Target Q6QNY0 in the descendant evidence is legitimate experimental grounding, not circularity. The current PAINT tree/node was not retrieved, so this review does not claim an independent reconstruction of the ancestral placement.

Summary: Endogenous BLOS3 co-purifies with BLOC-1.

Reason: PMID:15102850 directly reports endogenous human and mouse BLOS3 co-immunoprecipitation and size-exclusion co-fractionation with established subunits, supporting core complex membership.

Summary: BLOS3 functions as a BLOC-1 component in the cargo-sorting experiments.

Reason: PMID:17182842 includes BLOS3-deficient melan-rp cells and re-expression of human BLOS3, linking the subunit to the characterized complex. Retain the existing membership assertion with the independent endogenous and recombinant-complex evidence from PMID:15102850 and PMID:22203680; the abstract-only normal cache does not by itself show every membership assay.

Summary: Recombinant human BLOC-1 contains BLOS3.

Reason: PMID:22203680 uses eight human subunit constructs expressed in bacteria and characterizes an assembled heterooctamer containing BLOS3. Selected Methods and assembly Results were inspected in the official primary full text; this is evidence for human-protein complex membership despite the heterologous expression host.

Summary: Mouse orthology agrees with conserved BLOC-1 membership.

Reason: The electronic transfer from Q5U5M8 is independently corroborated by endogenous human BLOS3 complex isolation and recombinant human BLOC-1 assembly. No target-specific loss of complex membership is indicated.

Summary: The physical interaction evidence supports the intact BLOC-1 assembly.

Reason: Co-purification of the recombinant human subunits in PMID:22203680 supports BLOS3 membership in the octamer. The pallidin-Cappuccino-BLOS1 and dysbindin-Snapin-BLOS2 subcomplexes described in that study must not be mistaken for BLOS3-containing trimers.

Summary: BLOC-1 has a contextual role in neurite development.

Reason: The historical mouse donor annotation cites PMID:19546860. Selected full-text experiments quantify neurite deficits in pallidin-deficient primary mouse hippocampal neurons; they support the assembled complex rather than a BLOS3-specific human assay. Retain the conserved subunit-level ISS as a non-core developmental role and do not transfer individual SNARE-binding activities to BLOS3.

Summary: Movement of whole melanosomes is not resolved by the inspected cargo-sorting assays.

Reason: GO:0032402 describes movement of melanosomes themselves. The recovered PMID:17182842 Methods, Results and Discussion instead establish Tyrp1 cargo delivery from endosomes toward melanosomes, already represented by GO:0035646. Human BLOS3 rescue in mouse melan-rp cells supports cargo sorting; it does not itself demonstrate movement of whole organelles. The exact basis of this experimental GOA assertion remains unresolved because figure images and supplementary localization evidence were not inspected. Retain UNDECIDED rather than removing the experimental assertion; no organelle-motor function is inferred. The inspected official ontology defines GO:0032402 as movement of melanosomes and GO:0035646 as movement of substances from endosomes to melanosomes; their displayed is_a ancestry does not make the former a parent of the latter. Thus this experimental row is not dismissed as an ancestor duplicate.

Summary: BLOS3 is part of the machinery for melanosome biogenesis.

Reason: PMID:15102850 identifies BLOS3 in BLOC-1 and the reduced-pigmentation mouse mutation. The statement-level organization annotation is coherent with the later human BLOS3 rescue and cargo-sorting evidence, rather than being inferred from disease necessity alone.

Summary: BLOC-1 architecture supports its role in melanosome organization.

Reason: PMID:22203680 characterizes the human octamer whose established function is melanosome biogenesis. Retain the NAS with corroborating target rescue/cargo-sorting evidence from PMID:17182842; the structural paper does not itself measure all stages of melanosome organization.

Summary: The inherited endosome-to-melanosome role is experimentally grounded on BLOS3.

Reason: The PTN001592525 IBA is consistent with the human BLOS3 complementation and BLOC-1 cargo-exit mechanism in PMID:17182842. The target itself appearing in WITH/FROM reflects descendant experimental evidence and is not circular. No new phylogenetic loss or altered node placement is asserted.

Summary: BLOS3 contributes to the machinery that delivers endosomal cargo to melanosomes.

Reason: PMID:17182842 demonstrates BLOC-1-dependent Tyrp1 exit from early endosomes; selected primary passages include human BLOS3 re-expression in mouse melan-rp cells. This supports a functional subunit in the sorting machinery, not BLOS3 as transported cargo. The 2017 correction concerns the Figure7f transferrin-recycling assay; it does not retract the cargo-sorting result used here.

Summary: BLOS3-containing BLOC-1 associates with AP-3.

Reason: Human HeLa membrane-extract immunoprecipitation with anti-BLOS3 in PMID:16837549 associates the assembled BLOC-1 complex with AP-3. In PMID:22203680, the recombinant eight-human-subunit complex pulls down endogenous AP-3 from human MNT1 and mouse melan-a lysates, with GST and GST-AP-2 negative controls. This corroborates the inherited complex association and is retained as non-core. The experiment does not test AP-3 binding after selective BLOS3 omission or rescue, and no BLOS3-specific binding interface or requirement is established. Whole-complex association therefore supports the existing contextual row without asserting autonomous BLOS3 binding or adding a required contribution to this molecular activity to the core.

Summary: Human BLOC1S3 deficiency disrupts pigmentation.

Reason: PMID:16385460 documents oculocutaneous hypopigmentation and abnormal melanosome distribution in affected individuals. Retain the broad pigmentation phenotype as non-core; the core summary specifies endosomal cargo delivery and organelle biogenesis.

Summary: The PAINT synaptic-vesicle-transport assertion is retained as a contextual complex role.

Reason: The PTN001592527 annotation is compatible with BLOC-1-dependent delivery of vesicular cargo from cell bodies toward synapses in PMID:21998198. Its experimental context is distinct from the pigment-cell core. The current node/tree could not be inspected; neither a small descendant list nor missing direct human BLOS3 experiments establishes a phylogenetic error, so no propagation failure is asserted.

Summary: The electronic neuronal transport transfer is plausible but contextual.

Reason: The Q5U5M8 donor pathway, historically linked to PMID:21998198, concerns BLOC-1-dependent cargo delivery. The inspected experiments perturb other BLOC-1 subunits and do not show BLOS3 acting as a vesicle motor. Retain the conserved complex contribution outside the principal core summary.

Summary: The curator-mediated mouse neuronal transfer is retained outside the core.

Reason: A conserved BLOC-1 contribution to anterograde synaptic cargo delivery is compatible with PMID:21998198. This ISS retains its inferential scope: assembled-complex function is supported, while a BLOS3-specific neuronal mechanism and direct human neuronal experiments remain unestablished in the inspected evidence.

Summary: BLOS3 contributes to lysosome-related platelet granule biogenesis.

Reason: PMID:15102850 places BLOS3 in the BLOC-1 machinery needed for dense-granule biogenesis. The human BLOC1S3 family in PMID:16385460 has the concordant platelet storage/secretion phenotype. Retain the existing organization assertion as a core organelle-biogenesis role, without turning it into an independent platelet signaling activity.

Summary: The inter-ontology inference carries forward the transmembrane-mechanism error.

Reason: This row explicitly derives from GO:0008320. GO:0071806 concerns movement of protein across a membrane, whereas the inspected endosomal mechanism sorts membrane cargo between compartments. The source activity is rejected for that mechanistic mismatch; its logical biological-process consequence should also be removed. This conclusion does not require a historical wiki judgment or a claim about the current mouse donor record.

Summary: The specific axon-cytoplasm localization of BLOS3 remains unresolved.

Reason: GO:1904115 specifies cytoplasm within an axon. This electronic assertion derives from anterograde axonal and synaptic-vesicle transport terms. PMID:21998198 demonstrates BLOC-1-dependent cargo export from neuronal cell bodies and also discusses BLOC-1/AP-3 subunits detected in axons, dendrites and nerve-terminal complexes. The latter makes a neuronal complex location plausible, so a soma-sorting role does not establish absence from axons. However, the inspected experiments do not identify BLOS3 itself in axon cytoplasm, and the target-specific basis of the electronic localization was not recovered. Mark this precise compartment UNDECIDED rather than presenting the inferred location as established or rejecting it as biologically impossible.